Potential of Integrated [¹⁸F] Fluorodeoxyglucose Positron-Emission Tomography/CT in Identifying Vulnerable Carotid Plaques

Discussion

Integrated PET/MDCT scanners are now widely available and can provide information on plaque inflammation and composition in a single examination. This technique may be used to differentiate vulnerable from nonvulnerable carotid plaques, which may lead to a better risk stratification of patients with TIA/stroke with carotid atherosclerosis. This study compared ¹⁸F-FDG PET and MDCT findings between plaques ipsilateral to the side of symptoms and contralateral asymptomatic plaques causing <70% stenosis. Overall 5-year risk of (recurrent) ipsilateral stroke for the former is approximately 20%,¹⁰ while for the latter, it is approximately 2%.¹¹ In the present study, ¹⁸F-FDG PET only detected significant differences in patients who were imaged within 38 days. However, in this subgroup of patients, there was still substantial overlap in ¹⁸F-FDG uptake measurements.

In light of the error in TBR measurement (CV of 10.8%–12.1%), our findings suggest that selection of vulnerable versus nonvulnerable plaques on the basis of a TBR threshold may have a low sensitivity and/or specificity. In addition, we found strong positive correlations between ¹⁸F-FDG uptake in ipsilateral and contralateral asymptomatic plaques, which support the concept that atherosclerosis is a systemic inflammatory disease and may also explain why differences between both sides are small. MDCT detected larger vessel wall and LRNC volume in ipsilateral plaques, regardless of the time after symptoms. However, there was also substantial overlap between both sides. Moreover, interobserver variability of semiautomatic assessment of vessel wall and LRNC volume by MDCT, as previously reported by de Weert et al,⁶ is still considerable (CV of 23%–34% and 42%–58%, respectively), which may limit its clinical usefulness.

To date, only a few studies have compared ¹⁸F-FDG uptake between ipsilateral and contralateral asymptomatic plaques in relatively small sample sizes.^12,13 Using a stand-alone PET scanner, Rudd et al¹² performed a study in 8 patients with TIA with an ipsilateral carotid stenosis of at least 70%. The median time between symptoms and ¹⁸F-FDG PET imaging was 3.5 months.¹² Their analysis was limited to 6 of the 8 included patients, showing 34% higher ¹⁸F-FDG uptake on the symptomatic side.¹² However, this series of patients¹² may be too small to make any assumptions. Moreover, statins attenuate plaque inflammation on ¹⁸F-FDG PET,¹³ whereas the study of Rudd et al¹² was performed in an era when statin therapy was not as intensive or prevalent as it is at present. Font et al¹⁴ studied 15 patients with >70% stenosis, of whom 10 were defined as being symptomatic. In these 10 symptomatic patients who underwent an ¹⁸F-FDG PET scanning between 7 and 114 days (median, 33 days) after symptoms, there was no significant difference in ¹⁸F-FDG uptake between ipsilateral and contralateral asymptomatic plaques (1.19 versus 1.15, P = .185). However, due to the relatively limited sample size,¹⁴ no analysis with regard to timing of ¹⁸F-FDG PET could be performed.

In the present study, in which all patients were defined as symptomatic according to NASCET and European Carotid Surgery Trial criteria,^6,15 we did find a negative correlation between TBRs of ipsilateral plaques and the time after symptoms. This finding is in accordance with the results of a large histopathologic study⁸ showing that symptomatic carotid lesions remodel into more stable plaques with time after stroke. Sensitivity analysis indicated that ¹⁸F-FDG PET only detected significant differences if performed within 38 days after symptoms. Future independent studies should confirm our findings.

We found that MDCT identified significantly larger vessel wall and LRNC volume in ipsilateral plaques. Wintermark et al,¹⁶ who performed an MDCT study in 40 patients with stroke, also found larger vessel wall volume in ipsilateral plaques (1404.1 versus 1281.9 mm³, P = .020). They also found larger LRNC volumes, though this finding was not significant (24.9 versus 16.4 mm³, P = .196). In accordance, an MR imaging study by Saam et al¹⁷ demonstrated that plaques at the symptomatic side had larger mean LRNC areas (8.1 versus 6.3 mm², P = .2). A disadvantage of MDCT is that LRNC can only be adequately quantified in mildly calcified plaques.⁴ Other disadvantages of MDCT are that it cannot reliably distinguish intraplaque hemorrhage from LRNC, and fibrous cap status cannot be assessed. These parameters, which are also potential markers of plaque vulnerability, can be assessed by MR imaging.¹⁷ Whether MDCT or MR imaging may be more helpful in identifying vulnerable plaques can only be determined by prospective longitudinal studies.

Our study has several limitations. First, 90% of the included patients were on statin therapy, which may have attenuated plaque inflammation on ¹⁸F-FDG PET.¹³ However, the fact that most of the included patients with TIA/stroke used statins reflects current clinical practice. Second, the time between ¹⁸F-FDG injection and PET imaging was 1 hour. By increasing this interval, higher lesion-to-background contrast could have been achieved.¹² However, this was not possible due to too much patient discomfort. Third, ¹⁸F-FDG PET measurements may have been affected by partial volume errors. Future studies may use methods to reduce these errors.¹⁸ Fourth, we used a manual outlining method for ¹⁸F-FDG PET measurements, whereas a semiautomated method was used for MDCT measurements. The development and use of fully automated software may enhance reproducibility. Last, our study had a cross-sectional design. The true value of integrated ¹⁸F-FDG PET/MDCT in identifying vulnerable plaques can only be determined by performing a large prospective clinical trial.